Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease involves several organs. CD26 is a multifunctional molecule that has an extracellular domain with Dipeptidyl Peptidase IV activity, in which digest some crucial inflammatory molecules. On the other hand, CD26 plays quite an important role in T cell activation, and enhances the immune responses. This study, carried out to evaluate the level of CD26 gene expression in SLE patients. Methods: Forty-six SLE patients and 44 healthy controls voluntarily participated in this study. Based on the SLE disease activity index (SLEDAI), patients were divided into two subgroups, including patients with active disease (n = 24), and patients with inactive disease (n = 22). Moreover, according to renal involvement, patients were sub-grouped to patients with lupus nephritis (n = 17) and non-nephrotic patients (n = 29). CD26 mRNA level in peripheral blood cells was analyzed by quantitative RT-PCR.Results: CD26 mRNA expression 3.6 times increased in SLE patients in comparison with controls (P < 0.0001 ). However, no difference was found in the level of CD26 mRNA between SLE patients with active or inactive disease (P > 0.05 ). Even though, CD26 mRNA expression in patients with lupus nephritis was 2.76 times higher than non-nephrotic patients, but there was no statistical difference (P > 0.05 ).Conclusion: CD26 gene expression in peripheral blood cells of SLE patients significantly increased than controls. This increase was not affected by the disease activity, and did not show any significant correlation with complications in organs